Female Dietary Patterns and the Pathogenesis of NAFLD

In Europe as well as the United States, nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is strongly associated with obesity and type 2 diabetes mellitus (T2DM). Nonalcoholic fatty liver disease is defined as a hepatic manifestation of the metabolic syndrome. Being a very powerful and independent cardiovascular risk factor, NAFLD increases cardiovascular and overall mortality to a significant degree. The purpose of this review was to determine sex- and gender-specific differences in the prevalence and pathogenesis of NAFLD and delineate the specific characteristics of NAFLD as a systemic disease in men and women. Postmenopausal women and women with endocrine disorders such as the polycystic ovarian syndrome are at high risk of developing NAFLD. The increasing incidence of female NAFLD after menopause appears to be related to reduced estrogen and increased testosterone levels, as well as changes in the distribution of fatty tissue. Finally, the role of gender-specific nutrition patterns in the pathogenesis of NAFLD will be discussed. Fructose consumption from industrialized products is a promoter of NAFLD, depending on the total daily calorie intake of macronutrients. A higher level of health literacy and conscious food behavior have been noted among women of all age groups compared to males, which could play a role in the pathogenesis of NAFLD. Health professionals are confronted with the challenges of early diagnosis by the use of sensitive, reliable, and noninvasive diagnostic tools, including screening algorithms for high-risk persons and providing gender-specific nutritional support as a crucial element of treatment and disease prevention

Endostatin and osteopontin are elevated in patients with both coronary artery disease and aortic valve calcification

Background: The angiostatic factor endostatin (ES) plays an important role as mediator of angiogenesis. Elevated osteopontin (OPN) was associated with valve calcification in healthy individuals. The present study aimed to investigate ES and OPN levels in patients with both coronary artery disease (CAD) and aortic valve calcification (AVC). Methods and results: In total 224 non- or ex-smoking patients (161 male, mean age: 61.09 ± 11.02 years; 63 female: mean age: 67.49 ± 7.87 years) with angiographically verified and quantified CAD were recruited. Serum ES and plasma OPN levels were measured by ELISA and AVC was evaluated by a parasternal short axis view and quantified as non-, mild or moderate/severe. There was a stepwise increase of ES measurable with increasing severity of AVC, independent from age, BMI and CAD-severity (p = 0.018; F = 4.09). OPN also increased significantly with the grade of AVC severity (p = 0.029; F = 3.61) but was no longer significant when the co-variables (p = 0.31; F = 1.18) were inserted. Conclusions: This is the first study showing an association of ES with AVC in CAD-patients independent from age, BMI and CAD-severity which seems to be of distinct interest when trying to understand the process of heart valve calcification. OPN also correlates with AVC-severity but is mostly dependent on the age of the patients

Journal of Clinical Medicine / New Cardiovascular Biomarkers in Ischemic Heart DiseaseGDF-15, A Probable Predictor for Ejection Fraction

Background: Various biomarkers have been associated with coronary artery disease (CAD) and ischemic heart failure. The aim of this study was to investigate the correlation of serum levels of soluble urokinase-type plasminogen activator receptor (suPAR), growth differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), and soluble suppression of tumorigenicity 2 (sST2) with left ventricular ejection fraction (EF) in CAD patients and controls. Methods and Results: CAD patients were divided into three groups according to their EF as measured by the biplane Simpson method (5384%, 3152%, 30%). Overall, 361 subjects were analyzed. In total, 155 CAD patients had an EF of 5384%, 71 patients had an EF of 3152%, and 23 patients had an EF of 30% as compared to 112 healthy controls (age 51.3 9.0 years, 44.6% female). Mean ages according to EF were 62.1 10.9, 65.2 10.1, and 66.6 8.2 years, respectively, with females representing 29.0, 29.6, and 13.0%. suPAR, GDF-15, H-FABP, and sST2 values were significantly higher in CAD patients and showed an exponential increase with decreasing EF. In a multiple logistic regression model, GDF-15 (p = 0.009), and NT-brain natriuretic peptide (p = 0.003) were independently associated with EF. Conclusion: Biomarkers such as suPAR, GDF-15, H-FABP, and sST2 are increased in CAD patients, especially in highly impaired EF. Besides NT-proBNP as a well-known marker for risk prediction, GDF-15 may be an additional tool for diagnosis and clinical follow-up.(VLID)491673

Heart and Vessels / Long-term physical activity leads to a significant increase in serum sRAGE levels : a sign of decreased AGE-mediated inflammation due to physical activity?

There is growing evidence that low levels of the circulating soluble receptor of advanced glycation end products (sRAGE) are a valuable predictor of cardiovascular disease (CVD). The aim of this prospective study was to investigate the influence of long-term physical activity on serum sRAGE levels. 109 subjects were recruited, and 98 completed the study. Participants were asked to perform exercise within the calculated training pulse for 8 months. The performance gain was measured/quantified by bicycle stress tests at the beginning and end of the observation period. sRAGE was measured at baseline and after 2/6/8 months by ELISA. Backwards, multiple linear regression analysis was performed to investigate the association of co-variables age, sex, BMI, and performance at baseline, HbA1c, and lipoprotein a with baseline sRAGE levels. We identified BMI and lipoprotein a as significant predictors for baseline sRAGE levels. Compared to subjects with a performance gain 4.9% subjects with a gain > 5% showed a significant increase in sRAGE levels up to 22%. sRAGE serum levels correlate negatively with lipoprotein a levels and BMI and long-term physical activity leads to a significant increase in serum sRAGE levels (922%), whereby the sRAGE increase is most pronounced in subjects with initially low-performance levels, suggesting that in particular, these subject profit the most from increased physical activity. The sport-mediated increase of sRAGE might be a sign of decreased AGE-mediated inflammation and highlight the protective effect of sports on CVD and other disease which are at least partly mediated by an increased inflammation status. Clinical trials registration NCT02097199.(VLID)359103

Endurance training significantly increases serum endocan but not osteoprotegerin levels: a prospective observational study

Background Endocan (EN) was suggested a potential inflammatory and cardiovascular disease (CVD) marker which might also be involved in renal failure and/or renal failure-associated vascular events. It is not clear whether osteoprotegerin (OPG) is a pro- or anti-atherogenic factor, however, it is agreed upon that OPG is elevated in subjects with increased calcification status. The aim of the study was to investigate the influence of long-term physical activity on serum endocan (EN) and osteoprotegerin-levels. Methods One hundred nine subjects were told to increase their amount of physical activity for 8 months by performing 150min/week moderate or 75min/week vigorous exercise. Incremental cycle ergometer tests were performed at the beginning and the end of the study to prove and quantify the performance gain. Blood samples were drawn at baseline and every 2 months for the determination of EN and OPG. To investigate the difference between baseline and 8 months levels of EN and OPG we used a paired sample t-test. To investigate the significance of the tendency of the progression (baseline/2 months/4 months/6 months/8 months) we used a Friedman test. Results Thirty-eight female and 60 male subjects completed the study. In the group of 61 subjects who had a performance gain by >4,9% EN-levels increased from 146 110 to 196 238 pg/ml (p = 0,036) equivalent to an increase of 33,5% but there was no significant change in OPG (4,4 2,4 pmol/l vs. 4,3 2,1 pmol/l; p = 0,668). Conclusions Physical activity increases significantly EN-levels relativizing the status of EN as proinflammatory factor. EN should rather be considered as a mediator which is involved in several physiological (e.g., angiogenesis) but also pathological processes (e.g., CVD, tumour progression or endothelium-dependent inflammation) and whose expression can be significantly influenced by long term endurance training.(VLID)484340

International Journal of Medical Sciences / Sports and HDL-Quality Reflected By Serum Amyloid A and Surfactant Protein B

Background: The aim of this prospective study was to investigate the influence of long-term physical activity on HDL quality, reflected by serum amyloid A (SAA) and surfactant protein B (SPB). Methods and results: 109 healthy subjects were recruited, 98 completed the study. Participants perform within the calculated training pulse for 8 months. The performance gain was measured/quantified by bicycle stress tests at the beginning and end of the observation period. SAA and SPB were measured at baseline and after 4 and 8 months by ELISA. In contrary to HDL-quantity, there was no sports-induced change in SAA or SPB observable. However, significant predictors for SPB-levels were smoking status, BMI and weekly alcohol consumption and for SAA weekly alcohol consumption together with sex and hsCRP-levels. Conclusions: Long-term physical activity increases HDL-quantity but has no impact on HDL-quality reflected by SAA and SPB. Smoking is associated with higher SPB-levels and the weekly alcohol intake is associated with both higher SAA and SPB-levels suggesting a damaging effect of smoking and drinking alcohol on the HDL-quality. We assume that HDL-quality is at least as important as HDL-quantity when investigating the role of HDL in (cardiovascular) disease and should receive attention in further studies dealing with HDL.(VLID)486411

Physical Exercise Promotes DNase Activity Enhancing the Capacity to Degrade Neutrophil Extracellular Traps

(1) Background: An unhealthy lifestyle is a significant contributor to the development of chronic diseases. Physical activity can benefit primary and secondary prevention. Higher DNase activity is associated with favourable outcomes after cardiovascular (CV) events. In this study, we aimed to investigate the influence of consequent endurance exercise on DNase activity. (2) Methods: 98 subjects with at least one CV risk factor but the physical ability to perform endurance training were included. Individuals performed a bicycle stress test at the beginning and after 8 months to assess physical performance. In between, all participants were instructed to engage in guideline-directed physical activity. Blood samples were drawn in two-month intervals to assess routine laboratory parameters, cell-free DNA (cfDNA), and DNase activity. (3) Results: Prevailing CV risk factors were overweight (65.9%), a positive family history (44.9%), hypertension (32.7%) and smoking (20.4%). Performance changed by 7.8 ± 9.1% after 8 months. Comparison of baseline to 8 months revealed a decrease in cfDNA and an increase in DNase activity. This effect was driven by participants who achieved a performance gain. (4) Conclusions: Regular physical activity might improve CV health by increasing DNase activity and thereby, the capacity to lower pro-inflammatory signalling, complementing measures of primary and secondary prevention